Murakami Y, Zhang J, Eijgelshoven M H, Chen W, Carlyle W C, Zhang Y, Gong G, Bache R J
Department of Medicine and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Am J Physiol. 1999 Mar;276(3):H892-900. doi: 10.1152/ajpheart.1999.276.3.H892.
This study examined whether alterations in myocardial creatine kinase (CK) kinetics and high-energy phosphate (HEP) levels occur in postinfarction left ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examined in 19 pigs 6 wk after myocardial infarction was produced by left circumflex coronary artery ligation, and the results were compared with those from 9 normal pigs. Blood flow (microspheres), oxygen consumption (MVO2), HEP levels [31P magnetic resonance spectroscopy (MRS)], and CK kinetics (31P MRS) were measured in myocardium remote from the infarct under basal conditions and during dobutamine infusion (20 micrograms. kg-1. min-1 iv). Six of the pigs with LVR had overt congestive heart failure (CHF) at the time of study. Under basal conditions, creatine phosphate (CrP)-to-ATP ratios were lower in all transmural layers of hearts with CHF and in the subendocardium of LVR hearts than in normal hearts (P < 0.05). Myocardial ATP (biopsy) was significantly decreased in hearts with CHF. The CK forward rate constant was lower (P < 0.05) in the CHF group (0.21 +/- 0.03 s-1) than in LVR (0.38 +/- 0.04 s-1) or normal groups (0.41 +/- 0.03 s-1); CK forward flux rates in CHF, LVR, and normal groups were 6.4 +/- 2.3, 14.3 +/- 2.1, and 20.3 +/- 2.4 micromol. g-1. s-1, respectively (P < 0.05, CHF vs. LVR and LVR vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR and normal groups, whereas CHF hearts failed to respond to dobutamine. CK flux rates did not change during dobutamine in any group. The ratios of CK flux to ATP synthesis (from MVO2) under baseline conditions were 10.9 +/- 1.2, 8. 03 +/- 0.9, and 3.86 +/- 0.5 for normal, LVR, and CHF hearts, respectively (each P < 0.05); during dobutamine, this ratio decreased to 3.73 +/- 0.5, 2.58 +/- 0.4, and 2.78 +/- 0.5, respectively (P = not significant among groups). These data demonstrate that CK flux rates are decreased in hearts with postinfarction LVR, but this change does not limit the response to dobutamine. In hearts with end-stage CHF, the changes in HEP and CK flux are more marked. These changes could contribute to the decreased responsiveness of these hearts to dobutamine.
本研究检测了心肌梗死后左心室重构（LVR）过程中，心肌肌酸激酶（CK）动力学和高能磷酸（HEP）水平是否发生改变。在19头猪通过结扎左旋冠状动脉制造心肌梗死后6周，检测其心肌HEP和CK动力学，并将结果与9头正常猪的结果进行比较。在基础状态下以及多巴酚丁胺输注期间（20微克·千克⁻¹·分钟⁻¹静脉注射），测量梗死灶远端心肌的血流量（微球法）、耗氧量（MVO2）、HEP水平[³¹P磁共振波谱（MRS）]以及CK动力学（³¹P MRS）。研究时，6头患有LVR的猪出现了明显的充血性心力衰竭（CHF）。在基础状态下，CHF心脏各透壁层以及LVR心脏的心内膜下磷酸肌酸（CrP）与ATP的比值低于正常心脏（P<0.05）。CHF心脏的心肌ATP（活检）显著降低。CHF组的CK正向速率常数（0.21±0.03秒⁻¹）低于LVR组（0.38±0.04秒⁻¹）和正常组（0.41±0.03秒⁻¹）（P<0.05）；CHF组、LVR组和正常组的CK正向通量率分别为6.4±2.3、14.3±2.1和20.3±2.4微摩尔·克⁻¹·秒⁻¹（P<0.05，CHF与LVR比较以及LVR与正常组比较）。多巴酚丁胺使LVR组和正常组的速率 - 压力乘积增加一倍，而CHF心脏对多巴酚丁胺无反应。多巴酚丁胺输注期间，任何组的CK通量率均未改变。在基线状态下，正常、LVR和CHF心脏的CK通量与ATP合成（来自MVO2）的比值分别为10.9±1.2、8.03±0.9和3.86±0.5（每组P<0.05）；多巴酚丁胺输注期间，该比值分别降至3.73±0.5、2.58±0.4和2.78±0.5（组间P无显著性差异）。这些数据表明，心肌梗死后LVR心脏的CK通量率降低，但这种变化并不限制对多巴酚丁胺的反应。在终末期CHF心脏中，HEP和CK通量的变化更为显著。这些变化可能导致这些心脏对多巴酚丁胺的反应性降低。
